Gluconeogenesis Flashcards
What are the gluconeogenic substrates?
Amino Acids (Primary source)
Lactate
Glycerol
Where is pyruvate carboxylase found?
mitochondria of liver and kidney cells but not in muscle
What is the coenzyme for pyruvate carboxylase?
Biotin
How does oxaloacetate shunted from the mitochondria?
It’s reduced to Malate
What allosterically activates hepatic pyruvate carboxylase?
Where does this happen?
High levels of Acetyl CoA
Signal needs for OAA synthesis (fasting/starvation mode)
Mitochondria
When is pyruvate carboxylase inactive?
Under low levels of Acetyl CoA
Pyruvate is then oxidized in the TCA cycle
What enzyme converts OAA → PEP?
Where does it happen?
PEP-carboxykinase (PEPCK) using hydrolysis of GTP
Cytoplasm
What inhibits fructose 1,6-bisphosphatase?
Fructose 2,6-bisphosphate (product of PFK2 on the bifunctional enzyme) it’s an allosteric modifier
Hight levels of AMP (signal of low energy)
What activates fructose 1,6-bisphosphatase?
Hight levels of ATP and low levels of AMP
Fructose 2,6-bisphosphate is decreased by?
high levels of PKA because it binds to a G-protein and then increases cAMP which activates PKA. Once PKA is activated it phosphorylates the bifunctional enzyme and it turns OFF PFK2.
Where is glucose 6-phosphatase found?
In the liver and kidneys but not muscle (like pyruvate carboxylase)
What is Von Gierke’s Disease?
a glycogen storage disorder type I that has a defective glucose 6-phosphatase
What two methods does glucagon use to stimulate gluconeogenesis?
- Changes in allosteric effectors (lowers F 2,6-BP)
2. Covalent modification of enzyme activity (activates fructose 2,6-bisphosphatase by phosphorylation**
What is the metabolic effect of pyruvate kinase deficiency?
Inadequate ATP for maintaining ion pumps in RBC membrane resulting in loss of H2O
Damaged RBCs are subject to macrophage destruction in the spleen and leads to increased unconjugated bilirubin and increase in RBC 2,3-BPG proximal to the enzyme block
Increased 2,3-BPG shifts O2 binding curve right, decreasing O2 affinity
